Search

Recently the recruitment/migration of myeloid derived suppressor cells (MDSCs) to tumor microenvironment after chemotherapy has attracted much attention. To determine the detailed mechanism for the responses of MDSCs to these chemotherapies, we investigated the changes of galectin-3 and MDSCs in response to cisplatin(0.4 mg/kg, 4 mg/kg) treatment both in vivo and ex vivo. In the process of cisplatin, we assessed levels of galectin-3 and MDSCs in the Lewis lung cancer (LLC) bearing mice using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), immunofluorence and flow cytometry (FCM). The expression and changes of galectin-3 in the LLC cell line were detected by western blot, immunofluorence and ELISA. The ligand for galectin-3 on MDSCs and the chemotaxis of galectin-3 to MDSCs were confirmed using FCM and transwell. Parallel increased level of galectin-3 with the number of MDSCs in vivo was detected after cisplatin treatment. LLC cells expressed galectin-3 and cisplatin increased galectin-3 level in the culture medium. Furthermore, MDSCs were detected to express CD98, the ligand of galectin-3, and could be recruited by galectin-3. Our results suggested that the elevated expression of gelectin-3 in LLC tumor cells may contribute to the migration of MDSCs to the tumor microenvironment in response to cisplatin.

Objective: Since the debate still exists whether cisplatin-based and carboplatin-based chemotherapy are equally effective for advanced non-small-cell lung cancer (NSCLC), a meta-analysis of trials was performed to compare the cisplatin-based with carboplatin-based regimens in first line chemotherapy of advanced NSCLC., Methods: A literature search was performed in PubMed database, the Cochrane Central Register of Controlled Trials (CENTRAL) database, the Physician Data Query (PDQ) database and the American Society of Clinical Oncology (ASCO) annual meeting abstracts in January 2007. The following keywords were used: "non small cell lung cancer," or "Carcinoma, Non-Small-Cell Lung". Reference lists of original articles and review articles were also examined. The published languages and years were not limited. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed., Results: Eighteen randomized controlled trials (6906 patients) were identified from 4240 reports. The intention to treatment (ITT) analysis demonstrated that the cisplatin-based regimens had a higher overall response rate in comparison with carboplatin-based regimens (RR, 0.91; 95%CI, 0.84-0.99; P=0.02). However, the 1-year survival rate for the two platinum-based regimens were comparable (RR, 1.00, 95%CI, 0.94-1.07; P=0.93), Both subgroup analysis comparing the doublet or triplet regimens of cisplatin or carboplatin in combination with new agents and the same agents had achieved the same results. Cisplatin-based chemotherapy led to more frequent grade 3 or 4 of nausea and vomiting, and nephrotoxicity (OR, 0.39; 95%CI, 0.30-0.52; P<0.00001 and OR, 0.31; 95%CI, 0.17-0.56; P=0.0001), while carboplatin-based chemotherapy inclined to developing more grade 3 or 4 thrombocytopenia, however, there were no statistical significance (OR, 1.63; 95%CI, 0.94-2.82; P=0.08). The risk of grade 3 or 4 anemia, neutropenia and neurotoxicity was almost comparable between the two arms (OR, 0.78; 95%CI, 0.59-1.02; P=0.07; OR, 1.08; 95%CI, 0.80-1.45; P=0.61 and OR, 1.59; 95%CI, 0.81-3.14; P=0.18, respectively). The subgroup analyses of the comparison between the doublet or triplet regimens of cisplatin and carboplatin in combination with the same agents, respectively, also achieved similar results, with the exception of thrombocytopenia between the two groups (OR, 1.94; 95%CI, 1.47-2.68; P<0.00001), which showed statistically significant. Cisplatin arm inclined to causing more treatment-related deaths compared as carboplatin arm, but there was no statistical significance (OR, 0.70; 95%CI, 0.48-1.02; P=0.06)., Conclusion: Given cisplatin-based regimens had a higher overall response rate as compared with carboplatin-based regimens, there was not a survival advantage in the cisplatin group. Therefore, the toxicity profile might play an important role in decision to choose cisplatin-based or carboplatin-based regimens.

Abstract: Objective: Whether platinum plus gemcitabine or vinorelbine are equally effective in the treatment of advanced non-small-cell lung cancer (NSCLC) is still controversial, a meta-analysis was performed to compare the gemcitabine plus platinum with vinorelbine plus platinum regimens in first-line treatment of advanced NSCLC. Methods: A literature search was performed in PubMed database, the Cochrane Central Register of Controlled Trials (CENTRAL) database, the Physician Data Query (PDQ) database, EMBASE and the American Society of Clinical Oncology (ASCO) annual meeting abstracts. The following keywords were used: “non small cell lung cancer,” or “Carcinoma, Non-Small-Cell Lung”. Reference lists of original articles and review articles were also examined. The published languages and years were not limited. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Endpoints were overall survival, overall response, and toxicity. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates were two-sided. Results: Nine randomized controlled trials involving 2186 patients were identified from 453 reports. They were all published as full-text articles. The intention-to-treatment (ITT) analysis demonstrated that the patients with gemcitabine plus platinum regimens had an equal overall response rate in comparison with vinorelbine plus platinum regimens (RR, 0.91; 95%CI, 0.81–1.03; P =0.15). Furthermore, the 1-year survival rate for the two platinum-based regimens were comparable (RR, 1.06; 95%CI, 0.96–1.18; P =0.27). Subgroup analysis comparing the cisplatin plus gemcitabine or vinorelbine had achieved the same results. Vinorelbine plus platinum regimens led to more frequent grade 3 or 4 of neutropenia, nephrotoxicity, constipation and phlebitis (OR, 0.37; 95%CI, 0.26–0.52; P <0.00001; OR, 0.38; 95%CI, 0.25–0.57; P <0.00001; OR, 0.50; 95%CI, 0.27–0.92; P =0.03 and OR, 0.13; 95%CI, 0.05–0.32; P <0.00001, respectively), while gemcitabine plus platinum chemotherapy inclined to developing more grade 3 or 4 thrombocytopenia (OR, 11.37; 95%CI, 4.56–28.38; P <0.00001). The incidence of grade 3 or 4 anemia, nausea and vomiting were almost comparable between the two arms (OR, 1.12; 95%CI, 0.62–2.02; P =0.71 and OR, 0.72; 95%CI, 0.41–1.28; P =0.27, respectively). Similar results were also achieved in subgroup analyses between the gemcitabine and vinorelbine in combination with the cisplatin. Conclusion: It could be concluded that the efficacy were similar between the platinum plus gemcitabine or vinorelbine regimens. The choice of platinum plus gemcitabine or vinorelbine depends on the toxicity of the drugs and patients’ tolerance. [Copyright &y& Elsevier]